title: Identification of BRCA1-deficient ovarian cancers.
abstract: OBJECTIVE
  It is believed that 24-40% of ovarian cancers have dysfunction in the BRCA1 or BRCA2 (BRCAness) genes, due to either inherited or somatic mutations or due to epigenetic inactivation. Demonstration of ovarian cancers with BRCAness is becoming important both due to the possibility of offering genetic counseling and due to beneficial effects of polyadenosine diphosphate ribose polymerase inhibitor treatment in this group. As DNA sequencing is expensive and time consuming, efforts have been devoted to develop more indirect methods for BRCA screening that can improve the selection of patients for sequence-based BRCA testing.
  
  
  METHODS
  BRCA1 immunohistochemistry, fluorescence in situ hybridization (FISH) and methylation analyses were performed on formalin-fixed, paraffin-embedded ovarian cancer tissue.
  
  
  METHODS
  Fifty-four ovarian cancers; 15 BRCA1 cancers, four BRCA2 cancers, 10 cancers from patients with a family history but no mutation detected, and 25 ovarian cancers with unknown BRCA1 status.
  
  
  RESULTS
  Abnormal BRCA1 immunohistochemistry was found to indicate BRCA mutations with a sensitivity of 80%, a specificity of 93% and an estimated positive predictive value of 73%. The FISH analyses supported the diagnosis in most cases. Methylation analyses could indicate BRCA deficiency in combination with one of the other methods.
  
  
  CONCLUSIONS
  BRCA1 immunohistochemistry is a promising screening method for BRCA1 mutation detection.
authors.affiliation: Clinical Genetics Pathology, Vejle Hospital, Vejle, Denmark. anne-bine.skytte@slb.regionsyddanmark.dk
authors.forename: Anne-Bine
authors.initials: AB
authors.lastname: Skytte
authors.forename: Marianne
authors.initials: M
authors.lastname: Waldstrøm
authors.forename: Anders Aamann
authors.initials: AA
authors.lastname: Rasmussen
authors.forename: Dorthe
authors.initials: D
authors.lastname: Crüger
authors.forename: Emma R
authors.initials: ER
authors.lastname: Woodward
authors.forename: Steen
authors.initials: S
authors.lastname: Kølvraa
mesh_terms: D019313:BRCA1 Protein / Q000172:deficiency* / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human